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- Title
Nuclear factor-E2-related factor 2 expression in liver is critical for induction of NAD(P)H:quinone oxidoreductase 1 during cholestasis.
- Authors
Aleksunes, Lauren M.; Slitt, Angela L.; Maher, Jonathan M.; Dieter, Matthew Z.; Knight, Tamara R.; Goedken, Michael; Cherrington, Nathan J.; Chan, Jefferson Y.; Klaassen, Curtis D.; Manautou, Jose E.
- Abstract
Bile duct ligation (BDL) causes hepatocellular oxidative stress and injury. The transcription factor nuclear factor-E2-related factor (Nrf2) induces expression of numerous genes including NAD(P)H:quinone oxidoreductase 1 (Nqo1) during periods of oxidative stress. Therefore, we hypothesized that BDL increases liver expression of mouse antioxidant genes in an Nrf2-dependent manner. BDL or sham surgeries were performed on male C57BL/6, Nrf2-null, and wild-type mice. Livers were collected at 1, 3, and 7 days after surgery for analysis of messenger ribonucleic acid (mRNA) levels of Nrf2-responsive genes as well as Nqo1 protein and activity. BDL increased mRNA expression of multiple Nrf2 genes in mouse liver, compared to sham-operated controls. Follow-up studies investigating protein expression, enzyme activity, and Nrf2 dependency were limited to Nqo1. Nqo1 protein expression and activity in mouse livers was increased 2- to 3-. and 4- to 5-fold at 3 and 7 days after BDL, respectively. Studies also showed that BDL increases Nqo1 mRNA. protein expression, and enzyme activity in livers from wild-type mice, but not in Nrf2-null mice. In conclusion, expression of Nrf2-dependent genes is increased during cholestasis. These studies also demonstrate that Nqo1 expression and activity in mouse liver are induced via an Nrf2-dependent mechanism.
- Subjects
BILE ducts; OXIDOREDUCTASES; TRANSCRIPTION factors; ENZYMES; MESSENGER RNA; BILIARY tract
- Publication
Cell Stress & Chaperones, 2006, Vol 11, Issue 4, p356
- ISSN
1355-8145
- Publication type
Article
- DOI
10.1379/CSC-217.1